title: Structure of dual receptor binding to botulinum neurotoxin B.
abstract: Botulinum neurotoxins are highly toxic, and bind two receptors to achieve their high affinity and specificity for neurons. Here we present the first structure of a botulinum neurotoxin bound to both its receptors. We determine the 2.3-Å structure of a ternary complex of botulinum neurotoxin type B bound to both its protein receptor synaptotagmin II and its ganglioside receptor GD1a. We show that there is no direct contact between the two receptors, and that the binding affinity towards synaptotagmin II is not influenced by the presence of GD1a. The interactions of botulinum neurotoxin type B with the sialic acid 5 moiety of GD1a are important for the ganglioside selectivity. The structure demonstrates that the protein receptor and the ganglioside receptor occupy nearby but separate binding sites, thus providing two independent anchoring points.
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University, Stockholm 10691, Sweden.
authors.forename: Ronnie P-A
authors.initials: RP
authors.lastname: Berntsson
authors.forename: Lisheng
authors.initials: L
authors.lastname: Peng
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Pål
authors.initials: P
authors.lastname: Stenmark
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism*; D019274:Botulinum Toxins, Type A; D002151:Calorimetry; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D005732:Gangliosides / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D050861:Synaptotagmin II / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005732:Gangliosides; D050505:Mutant Proteins; D050861:Synaptotagmin II; C096323:rimabotulinumtoxinB; C021298:ganglioside, GD1a; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A